JP2787468B2 - Production method of cis-7-decene-4-olide - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION (Industrial Application Field) The present invention is found from the fragrance component of jasmine oil,
Cis-7-decene-4-olide (γ
Jasmolactone).

More specifically, the present invention has a jasmine-like aroma,
The following formula (1) useful as a fragrance compound The present invention relates to a novel process for producing cis-7-decene-4-olide represented by the formula:

(Prior Art) Conventionally, as a method for synthesizing cis-7-decene-4-olide, for example, Helv. Chim. Acta., 61, 990-997 (197)
8) has been proposed. According to this method, after acrolein is subjected to a condensation reaction with (Z) -3-hexenylmagnesium bromide to synthesize (Z) -nona-1,6-dien-3-ol, the compound is subjected to chromic acid oxidation to form (Z ) -Nona-1,6-dien-3-one to form a compound, which is then reacted with sodium cyanide to give (Z) -1-cyano-
6-nonen-3-one is synthesized, and the compound is further reacted with ethanol in the presence of p-toluenesulfonic acid to form ethyl (Z) -4-oxo-7-decenoate;
Furthermore, the compound is reduced and lactonized with sodium borohydride to synthesize (Z) -γ-jasmolactone.

(Problems to be Solved by the Invention) However, the above-mentioned conventionally proposed methods involve a large number of steps for producing the compound of the formula (1), and the yield of the target compound is not satisfactory. The use of toxic chromic acid causes safety and health problems, which are not always satisfactory and have problems to be solved.

Therefore, the present inventors have conducted intensive studies in order to solve the above-mentioned problems, and as a result, the following formula (5) 3-oxo-6-
By selecting nonionic esters as starting materials, the compound of formula (1) useful as a fragrance compound can be obtained in good yield in a short number of production steps without using highly toxic chromic acid,
The present inventors have discovered that they can be synthesized with high purity and completed the present invention.

Accordingly, an object of the present invention is to provide a method for producing the compound of the formula (1), which is useful as a fragrance compound, in an advantageous manner as compared with conventional synthesis methods.

(Means for Solving the Problems) According to the present invention, a 3-oxo-6-nonanoic acid ester of the following formula (5) is reacted with a halogenated acetic acid of the following formula (6) in an organic solvent in the presence of a base. The compound is reacted with an ester to form a 2- (1-oxo-4-heptynyl) succinic ester of the formula (4) described below, and the compound of the formula (4) is heated in an organic solvent in the presence of an acid. And hydrolytic decarboxylation to synthesize 4-oxo-7-decanoic acid esters of the following formula (3), and then subject the compound of the formula (3) to a cyclizing lactonization reaction with a metal hydride to form the following formula: Easily synthesizing the compound of the formula (1) of the present invention by synthesizing the decine-4-olide of the formula (2) and further partially reducing the compound of the formula (2) with hydrogen in the presence of a catalyst; Can be.

When the method for synthesizing the compound of the formula (1) of the present invention is represented by a reaction formula, for example, it can be represented as follows.

In the formula, R represents a methyl group and an ethyl group, and X represents a halogen atom. A method for synthesizing the compound of the formula (1) of the present invention will be described in detail below according to the above reaction formula.

The compound of the formula (5), which is a starting material of the present invention, is a compound described in the literature, and can be easily synthesized, for example, by subjecting an acetoacetate dianion to a condensation reaction with 2-pentynyl bromide. Specific examples of the compound of the formula (5) include methyl-3-oxo-6-noninoate and ethyl-3-oxo-6-noninoate.

In the above reaction formula, the compound of formula (5) is converted to the compound of formula (4)
The compound of formula (5) can be easily synthesized by subjecting the compound of formula (5) to a condensation reaction with the compound of formula (6) in an organic solvent in the presence of a base.

The above reaction is carried out, for example, in a temperature range of about 0 ° C to about 100 ° C, more preferably about 20 ° C to about 80 ° C, usually for about 1 hour to about
The reaction can be performed for 50 hours, more preferably about 5 hours to about 30 hours.

Examples of the compound of the formula (6) used in this reaction include methyl and ethyl esters of acetic acid in which halogen atoms such as fluorine, chlorine, bromine and iodine are substituted. Preferred specific examples are methyl bromoacetate and methyl Chloro acetate, ethyl bromoacetate, ethyl chloroacetate and the like can be mentioned. The amount of the compound of the formula (6) is, for example, in the range of about 1 mol to about 3 mol, more preferably about 1.2 mol to about 2.0 mol, per 1 mol of the compound of the formula (5). can do.

Specific examples of the base used in the above reaction include, for example, sodium hydride, sodium methoxide, sodium ethoxide, sodium amide, and the like.
The amount used is, for example, about 1 mol to about 3 mol, more preferably about 1.2 mol to 1 mol of the compound of the formula (5).
The range may be about 2.0 mol. Also,
As the type of the organic solvent used in this reaction, for example,
Examples thereof include tetrahydrofuran, methanol, ethanol, benzene, toluene, and dimethoxyethane. There are no particular restrictions on the amount of these organic solvents used, and for example, a range of about 2 to about 50 times by weight based on the compound of the formula (5) is more preferable.

After completion of the reaction, wash, extract, dry, concentrate,
If necessary, the compound of formula (4) can be obtained in good yield and purity by using a production means such as distillation.
Preferred specific examples of the compound of the formula (4) thus obtained include, for example, dimethyl 2- (1-oxo-4)
-Heptynyl) succinate and diethyl-2- (1-oxo-4-heptynyl) succinate.

In order to synthesize the compound of the formula (3) from the compound of the formula (4) obtainable as described above, the compound of the formula (4) is heated in an organic solvent in the presence of an acid to remove the compound by hydrolysis. It can be easily synthesized by performing a carbonic acid reaction.

This reaction can be performed, for example, in a temperature range of about 30 ° C. to about 100 ° C. for a reaction time of about 1 hour to about 50 hours.

Examples of the acid used in the above reaction include hydrochloric acid, sulfuric acid, hydrobromic acid, phosphoric acid and the like. The amount of the acid used may be, for example, about 1 mol to about 10 mol per 1 mol of the compound of the formula (4). Examples of the type of the organic solvent used in this reaction include methanol, ethanol, and the like. Preferred examples can be given. Specific examples of the compound of the formula (3) include methyl-4-oxo-7-decinoate and ethyl 4-
Oxo-7-decinoate can be mentioned.

In order to synthesize a compound of the formula (2) from a compound of the formula (3) obtainable by the above-mentioned method, the compound of the formula (3) is easily subjected to a cyclizing lactonization reaction with a metal hydride. Can be.

The above reaction can be performed in a temperature range of about -30 ° C to about 80 ° C, usually in a range of about 1 hour to about 30 hours.

Specific examples of the metal hydride used in this reaction include:
For example, sodium borohydride can be mentioned. The amount of the compound to be used is preferably, for example, in the range of about 0.25 mol to about 0.5 mol per 1 mol of the compound of the formula (3). This reaction can be performed in the presence of a solvent, and examples of the type of the solvent used include ethanol, methanol, isopropanol, diglyme, and water. The amount of these solvents used is about 2 to about the compound of the formula (3).
A preferred range is about 50 times by weight.

After completion of the reaction, the compound of the formula (2) can be obtained in a high yield and a high purity by washing, drying, concentrating and, if necessary, purifying using a method such as column chromatography, according to a conventional method. .

In the above reaction scheme, to synthesize the compound of the formula (1) of the present invention from the compound of the formula (2) obtainable as described above, the compound of the formula (2) is hydrogenated in the presence of a catalyst. It can be easily performed by partial reduction.

The above reaction can be performed, for example, in a temperature range of about 0 ° C to about 50 ° C, and more preferably in a range of about 10 ° C to about 30 ° C. There is no particular limitation on the reaction time, and the point where the theoretical amount of hydrogen has been absorbed may be used as the end point of the reaction. Hydrogen pressure is, for example, about 1 kg / cm ² to about 50 k.
g / cm ² range, preferably about 5 kg / c
m ² ~ about 10 kg / cm ² approximately ranges are often employed.

Specific examples of the catalyst used in the above reaction include a Lindlar type catalyst and a P2-nickel catalyst.
The amount of these catalysts can be appropriately changed, but the formula (2)
Is preferably about 1 to about 30% by weight,
More preferably, it is about 2 to about 10% by weight.

Further, the above reaction can be performed in the presence of an organic solvent,
Specific examples of the organic solvent used include methanol, ethanol, hexane, and toluene.
The use amount of these organic solvents is not particularly limited, but may be about 2 to about 50 times the weight of the compound of the formula (2).

After completion of the reaction, the used catalyst is filtered off and distilled under reduced pressure to obtain the compound of the formula (1) in good yield and good purity.

Hereinafter, the present invention will be described in detail with reference to examples.

Examples Example 1 Synthesis of dimethyl-2- (1-oxo-4-heptynyl) succinate [compound of (4)] A flask is charged with 14.5 g (0.36 mol) of 60% sodium hydride and 500 ml of tetrahydrofuran. A solution of 55 g (0.30 mol) of methyl 3-oxo-6-noninoate in tetrahydrofuran for 30 minutes under ice-water cooling (5 to 10 ° C.)
00 ml is added dropwise and stirred for a further 30 minutes. Next, 5-10 ° C
Takes 30 minutes with 55 g of methyl bromoacetate (0.36
Mol) in 100 ml of tetrahydrofuran. After the dropwise addition, the reaction is further stirred at room temperature for 20 hours. After completion of the reaction, the reaction product is neutralized, extracted with ether, washed, dried and concentrated. The obtained residue was distilled to obtain 61 g of a pure compound of the formula (4).

Yield: 80% Boiling point: 140 ° C. to 150 ° C./1 mmHg Example 2 Synthesis of methyl-4-oxo-7-decinoate [compound of formula (3)].

A flask was charged with 200 g of 6N hydrochloric acid, 400 g of methanol and 60 g (0.236 mol) of dimethyl 2- (1-oxo-4-heptynyl) succinate, and refluxed (75 ° C.).
The mixture is stirred and reacted for 15 hours. At the end of the reaction, the product is poured into saline and extracted with ether. The ether layer is washed with water, dried and concentrated. The obtained residue was further distilled to obtain 34.7 g of a pure compound of the formula (3).

Yield: 75% Boiling point: 112 ° C. to 115 ° C./1 mmHg Example 3 Synthesis of 7-decyne-4-olide [compound of formula (2)].

3.0 g (0.08 mol) of sodium borohydride in the flask
And 100 ml of 95% ethyl alcohol. Into this, 50 ml of a 95% ethyl alcohol solution of 30 g (0.15 mol) of methyl-4-oxo-7-decinoate is added dropwise over 30 minutes under ice-water cooling (5 to 10 ° C.). After dropping, further at room temperature 15
Stir for hours to react. After completion of the reaction, the reaction product is neutralized and extracted with ether. Wash, dry and concentrate the ether layer. The obtained residue was purified by silica gel column chromatography (n-hexane: ethyl acetate: 3: 1) to obtain 16.4 g of a pure compound of the formula (2).

Yield: 66% Boiling point: 123 ° C. to 124 ° C./1 mmHg Example 4 Synthesis of cis-7-decene-4-olide [compound of the formula (1)] 6 g of 7-decyne-4-olide in a 300 ml autoclave.
(36 mmol), methanol 10 ml, Lindlar catalyst 0.6 g
And 0.6 g of quinoline. At room temperature, hydrogen pressure 0.5-5kg
The hydrogenation reaction is performed under the condition of / cm ² . The reaction is terminated when the theoretical amount of hydrogen has been absorbed. After the completion of the reaction, the reaction product is discharged from the kettle and the catalyst is separated by filtration. The filtrate is washed, dried, concentrated and then distilled to obtain 5 g of a pure compound of the formula (1).
I got

Yield: 83% Boiling point: 106 ° C. to 110 ° C./1 mmHg (Effect of the Invention) The present invention provides a novel cis-7-decene-4-olide (γ-jasmolactone) represented by the above formula (1). To provide a simple manufacturing method. The production method is based on the formula (5)
The compound of the formula (1) is synthesized from oxo-6-nonanoic acid esters as a starting material in a short production step in a high yield and a high purity. Further, the compound of the formula (1) is contained in jasmine oil, and is useful as a raw material for preparing a jasmine-like fragrance composition.

──────────────────────────────────────────────────続 き Continued on front page (58) Field surveyed (Int.Cl. ⁶ , DB name) C07D 307/32 CA (STN) REGISTRY (STN)

Claims (1)

(57) [Claims] 1. The following formula (5) In the formula, R represents a methyl group or an ethyl group, and a 3-oxo-6-nonanoic acid ester represented by the following formula (6) in an organic solvent in the presence of a base: In the formula, R represents a methyl group and an ethyl group, X represents a halogen atom, and a condensation reaction with a halogenated acetic acid ester represented by the following formula (4) In the formula, R represents a methyl group and an ethyl group, to form 2- (1-oxo-4-heptynyl) succinic acid esters represented by the formula: and reacting the compound of the formula (4) with an acid in an organic solvent. Heated in the presence to cause hydrolysis and decarboxylation reaction, the following formula (3) In the formula, R represents a methyl group and an ethyl group, to form 4-oxo-7-decanoic acid esters represented by the following formula. Then, the compound of the formula (3) is subjected to a cyclizing lactonization reaction with a metal hydride. The following equation (2) Wherein the compound of formula (2) is partially reduced with hydrogen in the presence of a catalyst to form 7-decyne-4-olide represented by the following formula (1): A method for producing cis-7-decene-4-olide represented by the formula: